Originally published as: Ina Tammer, Kathrin Tintelnot, Rüdiger

Originally published as: Ina Tammer, Kathrin Tintelnot, Rüdiger

Originally published as:
Ina Tammer, Kathrin Tintelnot, Rüdiger C.
Braun-Dullaeus, Christian Mawrin, Cordula Scherlach, Dirk Schlüter, Wolfgang König,
Infections due to Pseudallescheria/Scedosporium species in patients with advanced HIV
disease — a diagnostic and therapeutic challenge, International Journal of Infectious Diseases,
Volume 15, Issue 6, June 2011, Pages e422-e429, ISSN 1201-9712.
DOI: 10.1016/j.ijid.2011.03.004
This is an author manuscript.
The definitive version is available at: http://www.sciencedirect.com/
Infections due to Pseudallescheria/Scedosporium
species in patients with advanced HIV disease —
a diagnostic and therapeutic challenge
Ina Tammera, Kathrin Tintelnotb, Rüdiger C. Braun-Dullaeusc, Christian Mawrind,
Cordula Scherlache, Dirk Schlütera, Wolfgang Königa
a
Institute of Medical Microbiology, Otto-von-Guericke University, Leipziger Str. 44, 39
120 Magdeburg, Germany
b
Division of Mycology, Robert Koch Institute, Berlin, Germany
c
Internal Medicine, Department of Cardiology, Angiology, and Pneumology, Ottovon-Guericke University, Magdeburg, Germany
d
Institute of Neuropathology, Otto-von-Guericke University, Magdeburg, Germany
e
Institute of Neuroradiology, Otto-von-Guericke University, Magdeburg, Germany
Summary
Objectives: The aim of this study is to highlight the importance of infections caused by members of
the genera Pseudallescheria/Scedosporium in HIV-positive patients.
Methods: We describe a case of a fatal scedosporiosis in a treatment-naïve HIV patient and review all
previously reported cases of pseudallescheriosis/scedosporiosis from a search of the PubMed and
Deutsches Institut für Medizinische Dokumentation und Information (DIMDI) databases, applying the
terms ‘Pseudallescheria’, ‘Scedosporium’, ‘Allescheria’, ‘Monosporium’, ‘Petriellidium’, ‘boydii’,
‘prolificans’, ‘inflatum’, cross-referenced with ‘HIV’ and ‘AIDS’.
Results: Detection of Scedosporium and Pseudallescheria species has been reported in 22 HIVpositive patients. Fourteen isolates belonged to the Pseudallescheria boydii complex and eight to
Scedosporium prolificans. Invasive scedosporiosis (IS) was proven in 54.5% of the patients. Among
them dissemination was observed in 66.7%. Pseudallescheria/Scedosporium species were mainly
isolated from male individuals. Patients with proven IS showed CD4+ cell counts <100/μl and a higher
co-infection rate as compared to colonized patients. Patients with central nervous system (CNS)
manifestations showed CD4+ cell counts <50/μl. The mortality rate for patients with proven IS was
75% and was 100% for patients with dissemination/CNS manifestations. The fatality rate for patients
treated with antifungal drugs plus surgery was lower compared to patients treated with antimycotic
agents alone.
Conclusions: IS only occurred in HIV-positive patients with a strongly impaired immune system. The
survival rates of patients with advanced HIV disease and invasive scedosporiosis can be improved by
rapid diagnosis by biopsy and requires complex therapy with a combination of active antifungal drugs,
surgery and supportive immune augmentation.
1. Introduction
Opportunistic mould infections have been considered an infrequent complication of the HIV disease.
Pulmonary aspergillosis, listed as an opportunistic infection in HIV-infected adults and adolescents by
the Centers for Disease Control and Prevention (CDC), is the most frequently diagnosed clinical
1
feature in this risk group. Reports on diseases caused by other species such as zygomycetes and
Pseudallescheria/Scedosporium species are rare. Nevertheless, in retrospective autopsy studies, a
2
substantial number of fatal cases have been characterized following missed ante-mortem diagnosis.
In this article, we present a case of a cerebral infection due to Scedosporium apiospermum in a patient
with AIDS. Based on a literature review we highlight the importance of this fungal organism and
related species, most frequently resistant to amphotericin B, as causes of life-threatening infections in
individuals with advanced HIV disease.
2. Case report
A 31-year-old cachectic woman was admitted to a secondary hospital because of progressive
neurological symptoms without further specification (June 2007). Based on these symptoms, a positive
Toxoplasma antibody titer, and typical contrast-enhanced lesions on magnetic resonance imaging
(MRI), cerebral toxoplasmosis was suggested. Toxoplasmosis, cachexia, and pharyngeal candidiasis
were highly suggestive of an HIV infection, which was confirmed by an HIV-1 RNA level of 306 000
copies/ml and a CD4+ cell count of 31 cells/μl. Toxoplasma encephalitis (TE) was first treated with
pyrimethamine, sulfadiazine, folic acid, and corticosteroids. Sulfadiazine was changed to clindamycin
because of an allergic skin reaction. Further diagnoses were cytomegalovirus (CMV) reactivation
diagnosed by CMV pp65 antigenemia, and herpes simplex virus (HSV) reactivation confirmed by
positive PCR from blood samples. The HSV infection was treated with intravenous acyclovir therapy.
Antiretroviral therapy (ART) was initiated with abacavir/lamivudine and ritonavir-boosted amprenavir.
The Candida albicans pharyngitis was treated with fluconazole. The patient responded well to the
therapy, resulting in a decrease in the neurological symptoms, a reduction in the cerebral foci, a
decline in the HIV viral load to 117 copies/ml, and an increase in the CD4+ count to 150/μl. On day 53
after admission the patient was discharged from the hospital.
Three weeks later (day 74) the patient suffered from paresthesia, paresis of the left side, and reduced
taste sensation. She tended to tilt but had no fever. At admission to the University Clinic Magdeburg
9
the following parameters were apparent: C-reactive protein (CRP) 21.5 mg/l, leukocytes 12.9 × 10 /l,
CD4+ cell count 16 cells/μl, HIV viral load negative. MRI showed multiple foci localized in the
cerebrum, cerebellum, and in the basal ganglia concordant with TE (Figure 1). Neurological symptoms
were considered as a side effect of the pyrimethamine therapy, resulting in a dose reduction to
100 mg/day. ART and antiparasitic therapy were continued as recommended. Clinical symptoms
declined and the woman was again discharged from hospital after 6 days (day 79).
Three weeks later (day 94) the patient was re-admitted to the hospital in a poor general condition
(days 94–114). A detailed examination showed paralysis of ocular movement, anisocoria, ataxia, and
hyperreflexia of the right side. Laboratory findings showed a CD4+ cell count of 45/μl and an HIV viral
load of 1120 copies/ml. The spinal fluid showed <5 cells/μl, an increased protein concentration of
746 mg/l (normal <450 mg/l), and a massive disturbance of the blood–brain barrier. PCR testing of the
cerebrospinal fluid (CSF) targeting HSV1/2-, CMV-, and Toxoplasma gondii-specific genes, as well as
screening tests for cryptococcal antigen were negative. MRI was unchanged.
Four weeks later (day 146) the patient became stuporous and had repeated convulsions. Her CD4+
count was 30/μl and HIV-1 RNA level was <40 copies/ml. Surprisingly, MRI revealed an additional
mass measuring 4 × 4 cm in the right basal ganglia, surrounded by a pronounced focal edema with
collapse of the ventricular system and a dislocation of the midline (Figure 2). A stereotactic biopsy was
performed. Microscopic examination from the biopsy revealed tissue invasion (Figure 3) by branched,
septated hyphae (Figure 4). Thus, a combined antifungal therapy with voriconazole and caspofungin
was started. The course of disease was further complicated by multi-organ failure. The patient died on
day 166. Permission for autopsy was denied.
2.1. Additional microbiological investigations
After 2 days of incubation at 37 °C a hyphomycete was detectable from cultures of the brain biopsy on
blood agar plates. Macro- and microscopic features allowed a primary classification to the
Pseudallescheria boydii complex. Based on sequence analysis of the internal transcribed spacer (ITS)
regions, the isolate was identified as S. apiospermum. In vitro susceptibility testing revealed minimum
inhibitory concentrations (MICs) of 2 μg/ml for voriconazole and >16 μg/ml for terbinafine, and a
minimal effective concentration (MEC) of 0.5 μg/ml for caspofungin after 48 h of incubation. The
isolate was deposited in the strain collection of the Reference Laboratory of Mycology (Robert Koch
Institut (RKI), Berlin, Germany) under the number RKI 07-0571. The sequence of the ITS regions was
submitted to the NCBI database and is available under GenBank accession number HQ857581.
3. Methods
Because of several taxonomic changes we searched PubMed and the Deutsches Institut für
Medizinische Dokumentation und Information (DIMDI) databases with the keywords:
‘Pseudallescheria’, ‘Scedosporium’, ‘Allescheria’, ‘Monosporium’, ‘Petriellidium’, ‘boydii’, ‘prolificans’,
‘inflatum’, cross-referenced with ‘HIV’ and ‘AIDS’ in order to identify published cases of
Pseudallescheria/Scedosporium sp in HIV-infected persons.
A total of 24 additional cases, 22 in English and two in Spanish, were identified as dealing with these
pathogens in HIV-infected people. The cases are listed in Table 1 in chronological order of the year of
publication. It must be noted that cases 12 and 15 describe the same patient; this is also the case for
cases 13 and 22. In addition, cases 23 and 24 most likely refer to the same patient. Hence these
cases were summarized and counted as one case each. Thus, a total of 22 case reports (including the
case presented here) were analyzed with regard to the following criteria: causative species, clinical
symptoms, manifestations of the disease, complications, concomitant diseases, laboratory findings,
treatment regime, and outcome, if available. Case 4 was only published as an abstract.
Invasive infections due to these pathogens are entitled ‘invasive scedosporiosis’ (IS). The cases were
defined as ‘proven’ according to the definitions of the European Organization for Research and
Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of
3
Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus group. Patients
without signs and symptoms of clinical disease were categorized as colonized, including those with
fungus ball formation in pre-existing cavities without demonstration of fungal elements in diseased
tissue.
The co-infection rate was calculated from the number of diseases per case.
Based on new morphological, physiological, and molecular data, the taxonomy of the fungi belonging
to the genera Pseudallescheria and Scedosporium has been revised in recent years. P. boydii and S.
apiospermum are now described as two distinct species grouped into the newly defined P. boydii
[4] and [5]
complex.
Scedosporium prolificans, formerly Scedosporium inflatum, is distantly related to the
P. boydii complex.
4. Results
Detection of Scedosporium and Pseudallescheria species has been reported in 22 HIV-positive
[6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26] and [27]
patients (Table 1).
Fourteen
isolates belonged to the P. boydii complex and eight to S. prolificans.
The most frequent portal of mould entry was the respiratory tract (68.2%). In 86.7% of these cases the
moulds were present in the lung and in 13.3% in the paranasal sinuses. Three of the 22 patients
(13.6%) suffered from otitis externa, whereas in four patients (18.2%) the portal of entry remained
unclear.
Invasive scedosporiosis was proven in 12 of the 22 patients (proven IS; 54.5%). Ten patients met the
criteria of ‘colonization’, including three patients harboring a fungus ball in pulmonary cavities. One
patient with fungus ball formation developed localized invasive infection, which was proven by
histology. One patient was co-colonized with two species, S. apiospermum and S. prolificans.
Proven invasive fungal infection was caused by members of the P. boydii complex in eight patients
and by S. prolificans in four patients.
IS was disseminated in eight of the 12 cases and was proven by either fungemia or autopsy (66.7%).
Five of these patients developed central nervous system (CNS) manifestations.
Patients suffering from proven IS had 3.6 opportunistic diseases per case, whereas patients who were
only colonized showed a co-infection rate of 2.0 on average (Table 2). Reactivation of members of the
family Herpesviridae and candidiasis were the most frequently reported opportunistic infections. These
were more frequent in patients developing disseminated rather than localized infections.
Co-isolation or infections due to Aspergillus species and Pseudomonas aeruginosa infections were
exclusively observed in patients with proven IS.
The clinical outcome of the patients was fatal in 14 out of the 22 cases (63.6%, Table 1). Nine of all
reported patients died as a result of their fungal disease, leading to a mortality rate of 40.9% (Table 3).
Among the patients with proven IS, 75% (n = 9/12) died, whereas 25% of the patients responded to
therapy and survived (n = 3/12). In one of these cases the cause of death remains unknown. All
survivors had localized infections caused by members of the P. boydii complex. In contrast, all patients
suffering from proven S. prolificans infections died.
CD4+ cell counts were available for 15 of the 22 patients (Table 2). Ten of the 15 patients had cell
counts <50/μl (66.7%). In addition, CD4+ counts <50/μl were reported from 62.5% of the patients with
proven IS and from 71.4% of the colonized patients. The mean CD4+ cell count of the colonized
patients was about three times higher than that of patients with proven IS. All patients with CNS
manifestations showed CD4+ cell counts <50/μl.
The HIV viral load was reported in seven of 22 patients (31.8%). Two of them were colonized and five
patients suffered from proven IS. Patients with proven localized infections had a ca. two-fold higher
viral load than colonized patients. Significant data about ART onset and virus resistances were not
available.
ART was reported in detail in seven of 17 cases (41.2%) with previously known HIV infection (Table
4). Five patients were ART-naïve because pseudallescheriosis/scedosporiosis was the first
manifestation of the AIDS disease. Two of them died before ART could be administered. No data were
available for 10 cases.
Altogether seven of the cases were published in the era before highly active antiretroviral therapy
(HAART) was introduced. Four of them suffered from proven IS, three patients were colonized. In
three of the cases with a proven IS fungal infection was the first manifestation of the HIV disease. All
patients with proven IS died.
Fifteen cases were reported since the introduction of HAART. Among them were eight patients with
proven IS and seven patients who were colonized. For two patients the detection of
Pseudallescheria/Scedosporium sp guided to the diagnosis of AIDS. Of the eight patients with proven
IS, three responded to therapy.
Antifungal treatment regimes (Table 4) were administered to nine of the 12 AIDS patients suffering
from proven IS owing to the isolation of Pseudallescheria/Scedosporium species from a clinical
specimen (75%). Five of these patients were treated with antifungal agents alone and four underwent
surgery in addition to antimycotic therapy. No patient was treated with surgery alone. Three patients
died before antifungal treatment could be started.
Granulocyte colony-stimulating factor (G-CSF) was administered in three cases, and granulocyte
macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-γ) were administered in
one case each (Table 4).
5. Discussion
Invasive or disseminated infections due to the genera Pseudallescheria/Scedosporium have been
[28], [29], [30], [31] and [32]
reported in immunocompetent and in immunocompromised patients.
HIV infection
per se has not been considered a major risk factor for mould infection, because the innate host
defense is impaired only in the late stage of AIDS disease. Risk factors associated with the
identification of Aspergillus sp in respiratory specimens from HIV-seropositive individuals have been
found to be neutropenia, a CD4+ count <30 cells/μl, corticosteroid use, and Pneumocystis jirovecii
33
infection. Since members of the P. boydii complex and S. prolificans show virulence and clinical
34
spectra similar to those of Aspergillus species, similar risk factors could be suggested. At the time
point of diagnosis of IS in our patient, her CD4+ cell count was <30/μl and the treatment regime of TE
included corticoids. Reviewing the published cases, CD4+ counts <50/μl did not differ significantly
between colonized and infected individuals. Nevertheless, patients with proven IS showed lower mean
CD4+ cell counts and a higher co-infection rate as compared to patients only colonized by
Pseudallescheria/Scedosporium species.
Corticosteroids have a profound effect on the distribution and function of neutrophils, monocytes, and
lymphocytes and are therefore reported to be associated with an increased risk of invasive
35
aspergillosis in allogeneic hematopoietic stem cell transplant (HSCT) recipients. In addition, in vitro
investigations have shown that corticosteroids directly stimulate the growth of Aspergillus fumigatus,
36
an effect not demonstrated for Pseudallescheria/Scedosporium species so far. Previous
corticosteroid treatment did not seem to influence the acquisition of Pseudallescheria/Scedosporium
sp as it was administered in only four of the 12 patients with subsequent development of proven IS.
Fluconazole prophylaxis given after cryptococcal disease did not prevent other mould infections like IS
because fluconazole is ineffective against Pseudallescheria/Scedosporium species.
Analysis of the cases regarding the gender distribution showed a marked preponderance of males
over females, resulting in a male/female ratio of 5:1 for patients with proven IS. Interestingly,
37
Mylonakis et al., who analyzed 342 cases of pulmonary aspergillosis in AIDS patients, observed a
male/female ratio of 4.9:1. As the gender distribution of HIV disease in Europe and Northern America
38
is approximately 3:1, a predisposition for the male is suggested.
Members of the P. boydii complex are ubiquitously distributed in soil and water, whereas S. prolificans
39
is primarily isolated from soil and plants. Furthermore, S. prolificans is geographically more restricted
than members of the P. boydii complex. Thus, members of the P. boydii complex were more common
in patients with advanced HIV disease as compared to S. prolificans. The origin of the patients
colonized or infected by S. prolificans correlates with known endemic areas in the northern part of the
[22] and [40]
Iberian Peninsula, Australia and the USA.
Infections have rarely been reported from other
[41] and [42]
countries.
Filamentous fungi enter the respiratory tract via inhalation; the skin, wounds, and eyes are infected by
43
direct inoculation. The respiratory tract, including the lung, was the most frequently reported portal of
entry for Pseudallescheria/Scedosporium sp in patients with advanced HIV disease. Interestingly,
members of the P. boydii complex infected the host either via the respiratory tract or the external
auditory canal, whereas S. prolificans exclusively infected the lung. In our patient, the mode of entry
remains unclear. Small foci can be unapparent during the initial stages of the infection and may not be
44
12
detected by radiographic means. Similar observations have been described by Nenoff et al., as
chest radiographs revealed no signs of pulmonary infiltration, but autopsy showed mycotic infiltrates in
the left upper lobe of the lung.
In persons exposed to a high environmental inoculum of spores and with underlying pulmonary
diseases, transient airway colonization may become persistent. Colonization of the respiratory tract
due to S. apiospermum and S. prolificans was extensively evaluated in cystic fibrosis patients and in
[22] and [45]
liver transplant recipients.
Our review shows that colonization of the airway tract is not a rare
event in AIDS patients. Interestingly, fungus ball formation in AIDS patients was exclusively caused by
members of the P. boydii complex, although the lack of cases with fungus ball formations by S.
prolificans may be due to the limited number of case reports. Nevertheless, in contrast to Aspergillus
species, the role of members of the P. boydii complex or S. prolificans as airway colonizers is not well
accepted and the risk for the development of invasive or disseminated diseases should not be
underestimated, especially when the immune system is impaired, as was demonstrated in case 23.
[26] and [27]
Thus, colonized patients with underlying immune diseases should be subjected to regular
follow-up evaluations.
As illustrated in our case, CNS involvement represents a devastating complication of
pseudallescheriosis/scedosporiosis. The species are frequently reported to exhibit a particular tropism
for the CNS, but the mechanisms of the host defense evasion and damage of the blood–brain barrier
[46], [47], [48], [49] and [50]
remain largely unexplained.
In this study, CNS manifestations were observed in
41.7% of the AIDS patients with proven IS. Since the rate of dissemination in previously healthy
patients, for example after near-drowning, is similar to the data presented here, immunosuppression
[51], [52] and [53]
appears not to be a precondition for CNS manifestations.
In our patient, TE was suspected
based on typical contrast-enhancing masses in the MRI, neurological symptoms, seropositivity for
Toxoplasma-specific IgG antibodies, and initial remission of clinical symptoms after administration of
antiparasitic therapy. Since similar lesions of different size were the most common finding reported
54
from CNS infections due to members of the P. boydii complex, a computed tomography (CT)-guided
needle biopsy at the first time of deterioration would have been required to confirm the diagnosis in our
patient.
Mimicking the clinical features of certain other important filamentous fungi,
Pseudallescheria/Scedosporium species cannot be distinguished from others by the use of histological
methods exclusively. Therefore, rapid identification of the infectious organism by molecular methods in
parallel to cultures is mandatory and necessary due to the poor response of the species to
[47], [55] and [56]
amphotericin B.
Mortality rates after invasive fungal infection are high, especially in patients with disseminated
infections. In this study we calculated a mortality rate of 75% for AIDS patients with proven IS. Similar
57
results were reported for P. boydii infections in solid organ transplant recipients. Moreover, the
mortality rates differed with respect to the causative agent. Fatality rates of invasive infections due to
S. prolificans were 100% compared with 75% for infections caused by members of the P. boydii
complex. In a study reviewing German S. prolificans cases, 92% of the patients developed a fatal
58
infection. The high fatality rate of S. prolificans infections may be caused by two facts: (1) conidia
contain melanin which has been related to the high affinity to the brain and (2) the species is
59
multidrug-resistant.
The majority of the members of the P. boydii complex are resistant to amphotericin B and terbinafine.
As Aspergillus species are known to be the most common cause of fungal infections, amphotericin B
is often used as first-line therapy. It is therefore important to distinguish Aspergillus species from
Pseudallescheria/Scedosporium sp in order to initiate an appropriate antifungal treatment. Miconazole
[60] and [61]
and voriconazole have shown low MIC values against the members of the P. boydii complex.
Today the intravenous administration of miconazole is limited by its high toxicity and in Germany by its
unavailability. Voriconazole is accepted as the gold standard because it has been used successfully in
62
the treatment of CNS infections due to members of the P. boydii complex. The clinical experience
with posaconazole against Pseudallescheria/Scedosporium sp is limited and this needs further
investigation.
In the presented case, voriconazole was combined with caspofungin. New echinocandins lack CNS
penetration, an effect also known from amphotericin B. The combination of caspofungin with
voriconazole significantly reduced colony counts in lung, liver, kidney and brain tissues in experimental
invasive aspergillosis in neutropenic guinea pigs, suggesting a penetration of the drugs into the CNS
63
via the impaired blood–brain barrier. For S. prolificans, synergistic effects of voriconazole with
[58], [64], [65] and [66]
terbinafine have been observed.
In our case study, no AIDS patient with S. prolificans
infection was treated with a combination of terbinafine plus azole, suggesting that this treatment option
is not well established.
Multiple studies have confirmed the beneficial effect of additional radical surgical debridement to
[46], [47] and [67]
reduce fungal burden.
This review demonstrates differences between the mortality rate of
patients treated with antifungal drugs alone and those treated with antifungal drugs plus surgery.
54
Similar observations have been reported by Kantarcioglu et al.
In this study, only three of the AIDS patients with proven IS responded to therapy. In all cases the
infections remained localized. All patients were infected with members of the P. boydii complex. Two
non-neutropenic patients underwent radical surgery plus antimycotic treatment. The other survivor did
not undergo surgery but was additionally treated with a complex immune-enhancing regime (G-CSF,
IFN-γ, GM-CSF). HAART was administered in two patients. The small number of successful clinical
outcomes from deep-seated S. prolificans infections supported the efficacy of voriconazole plus
[64], [65], [66] and [68]
terbinafine with or without surgery and a supportive immune-enhancing therapy.
The introduction of HAART in 1996 has significantly reduced the rates of opportunistic infections.
However, most of the proven cases of pseudallescheriosis/scedosporiosis in this review were reported
after 1996 (eight vs. four cases).
It has been reported that the receipt of HAART is associated with immune reconstitution disease (IRD)
69
or inflammatory syndrome (IRIS) in approximately 32% of patients. Due to a lack of information in the
reviewed cases we cannot comment on the occurrence of IRIS. For most of the cases, data on the
pre- and post-HAART CD4+ cells and HIV-RNA copies were not available.
In our case, an unusual course of the suggested TE could not be excluded. The patient was naïve to
ART at the time of diagnosis. She responded well to HAART, resulting in a rapid decrease in the HIV-1
RNA level and a rise in the CD4+ cell count. Thus it remains unclear whether HAART obscured an
existing scedosporiosis, or if this infection was acquired secondary to other opportunistic infections like
TE.
6. Conclusions
Members of the P. boydii complex and S. prolificans should be considered in the differential diagnosis
as potential causes of infections in patients with advanced HIV disease. Since cerebral lesions may be
caused by various pathogens or by the HIV disease itself, the rapid differentiation between HIVassociated diseases and opportunistic infections is a prerequisite for a successful target-related
treatment. Stereotactic CT-guided needle biopsy as early as possible is the most suitable approach to
confirm the diagnosis. Serological methods to detect scedosporiosis are not available. Histological
examination is necessary to differentiate between colonization and invasive infection, but is unsuitable
to identify the fungus. Microbiological investigation, including culture and molecular methods, is
indispensable for a correct diagnosis and to initiate an adequate therapy. Radical surgery, wherever
applicable, combined with a target-related antimycotic chemotherapy (voriconazole plus terbinafine in
the case of S. prolificans infections; voriconazole plus caspofungin against members of the P. boydii
complex) and adjunct immune stimulation advance the clinical outcome.
Acknowledgements
We thank Jaquelin Faerber, MD, for her skillful support.
Conflict of interest: All authors have no conflict of interest. This paper was written without any financial
support.
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Tables and Figures
Table 1. Pseudallescheria/Scedosporium infection in patients with HIV/AIDS: clinical characteristics
BAL, bronchoalveolar lavage; CNS, central nervous system; CSF, cerebrospinal fluid; NR, not
reported.
Table 2. Laboratory findings and concomitant diseases
IS, invasive scedosporiosis; CNS, central nervous system.
a
b
Herpesviridae = cytomegalovirus, herpes simplex virus type 1/2, varicella zoster virus.
Mycobacterium sp = M. tuberculosis, M. avium-intracellulare.
Table 3. Antifungal treatment and clinical outcome
IS, invasive scedosporiosis.
Table 4. Treatment regimes (available data)
IS, invasive scedosporiosis; CNS, central nervous system; G-CSF, granulocyte colony stimulating
factor; GM-CSF, granulocyte macrophage colony stimulating factor; PjP, Pneumocystis jirovecii
pneumonia.
Figure 1. MRI at day 75 after first admission. T2 transverse scan (Siemens Magnetom Vision 1.5 T):
multiple, rounded T2 hyperintense lesions on both sides of the basal ganglia, compatible with cerebral
toxoplasmosis.
Figure 2. MRI at day 148 after first admission. T2 transverse scan (Siemens Magnetom Vision 1.5 T):
new inhomogeneous, rounded mass of approximately 30 mm in diameter in the thalamus region and
the left lateral basal ganglia with perifocal edema and compression of the left lateral ventricle.
Figure 3. Histopathological examination. Necrotic and hemorrhagic brain tissue derived from a brain
biopsy, with demonstration of fungal elements using Grocott's methenamine silver stain; magnification
of ×200.
Figure 4. Microbiological examination of the cerebral tissue with Gram staining, showing branched
septate hyphae (black arrows); magnification of ×200.